Nearly two-thirds of the US population is either clinically overweight or obese and almost 10% of the population has adult-onset diabetes. Obesity and diabetes are central elements of a cluster of pathologies collectively referred to as "metabolic syndrome". Our Center of Biomedical Research Excellence (COBRE) at the Pennington Biomedical Research Center is leading an effort to enhance research on metabolic disease by recruiting accomplished senior investigators and promising young scientists who are mentored to independence by Center investigators. The Pennington COBRE involves five projects from outstanding junior faculty that employ a combination of cellular, molecular, and translational approaches to address questions ranging from neural mechanisms of glucose sensing and energy homeostasis, inflammatory mechanisms linked to adipogenesis, epigenetic programming in obesity, to regulation of mitochondrial biogenesis in adipocytes. Using a combination of in vivo, ex vivo and in vitro approaches, each project will pursue fundamental questions critical to regulation of energy homeostasis and the associated pathologies of metabolic disease linked to expansion of adipose tissue mass during development of obesity. The Specific Aims of our COBRE in Phase II are to further expand the critical mass of productive investigators engaged in obesity/diabetes research by (a) develop and retain outstanding new junior faculty from within the institution and mentor them to sustainable independent funding (b) recruit outstanding junior and senior faculty engaged in metabolic disease research that complement existing strengths of Center investigators;(c) develop and foster new opportunities for collaborative interactions with institutional colleagues engaged in clinical/translational research, (d) enhance utilization ofthe outstanding research infrastructure developed within the Cell Biology/Bioimaging and Genomics core facilities in Phase I through development of training modules and outreach activities. Our Phase II COBRE goals are to recruit 5 new faculty to the institution and mentor 10 junior faculty to independent funding as we continue to build a critical mass of scientists devoted to finding solutions to the expanding national health problem of metabolic disease.